Chromosomal Basis of Inheritence

The chromosome theory of heredity

Although it was suspected that genes were situated in chromosomes, no definite proof was there yet. Thomas H. Morgan, discovered a particular eye colour mutation in the fruit fly Drosophila melanogaster. Advantages of working with this fly were:

Quick reproduction, inexpensive to rear in laboratory and it had only 4 pairs of chromosomes. One pair being the sex chromosomes, were morphologically distinguishable from each other and the autosomes.

Morgan was able to show that eye colour mutation of fruit fly was inherited along with the X chromosome.
This suggested that a gene for eye colour was physically situated on that chromosome. This theory was later definitely proved by one of his students named Calvin B. Bridges.

Experimental Evidence Linking the Inheritence of genes to chromosomes

Wild type female with Red eyes

Mutant Male fly with white eyes

All progeny had Red eye colour

Progeny (F1) female fly with Red eyes

Progeny (F1) Male fly with Red eyes

All (100%) the daughters had Red eyes Only half (50%) the sons had Red eyes

X X P

X
W+ W+
Red Eyed Female

W
White Eyed male

F1

X
W+ W
Red Eyed Female

W+
Red Eyed male

F2

W+ W+
Red Eyed Female

W+ W
Red Eyed Female

W+
Red Eyed male

W
White Eyed male

F1

X
W+ W
Red Eyed Female

W+
White Eyed male

F2

W+ W+
Red Eyed Female

W+ W
White Eyed Female

W+
Red Eyed male

W
White Eyed male

Cross between a heterozygous female and a hemizygous mutant male

X X P

X
W+ W+
White Eyed Female

W
Red Eyed male

F1

X
W+ W
Red Eyed Female

W+
White Eyed male

F2

W+ W+
White Eyed Female

W+ W
Red Eyed Female

W+
White Eyed male

W
Red Eyed male

Cross between a homozygous mutant female and a hemizygous wild-type male

Morgan and his students soon identified other X-linked genes in Drosophila. Simple breeding experiments demonstrated that recessive mutations of these genes were transmitted along with the X chromosome. They found out that many genes were located on the X-chromosome. They also found genes not on the X-chromosome. These genes followed the Mendelian Principle and did not segregate with sex (unlike gene of the eye colour). Morgan correctly concluded : Such genes were located on one of the three autosomes in the Drosophila genome. Thus each Drosophila chromosome appeared to contain a different set of genes. Morgans team experimented with relationship among genes on a particular chromosome. Cytological study already indicated that chromosomes were long threadlike structures. They showed that genes were situated at different loci (sites) on the linear structure. They pioneered the first genetic mapmaking and studying the physical structure of chromosomes. All their observations lead to the Chromosome Theory of Heredity.

Chromosome Theory of Heredity All genes are located on the chromosomes. Mendels principles could be explained by the transmission properties of chromosomes during reproduction. This theory stands as one of the most important achievements in Biology.

Proof of the Chromosome Theory by Nondisjunction.

Morgan showed that the gene for eye colour was on the Xchromosome in Drosophila by correlating the inheritence of the gene with the transmission of X-chromosome during reproduction. Later, his student C. B. Bridges secured proof of the chromosome theory by showing that exceptions to the rules of inheritence could also be explained by chromosome behaviour. Bridges performed Morgans experiments on a larger scale.

Bridges crossed white-eyed female Drosophila with red-eyed males and examined the F1 progeny. As expected, nearly ALL the F1 flies were either redeyed females or white-eyed males. However, he found a few exceptions: A few were white-eyed females and red-eyed males. He crossed between these exceptional males and females and got the following results: 1. The exceptional males were ALL proved to be sterile. 2. However, the exceptional females were fertile.

3. When these fertile white eyed females were crossed with normal red-eyed males, they produced many progeny, including large numbers of white-eyed daughters and redeyed sons. 4. Thus, the exceptional F1 females, though rare in their own right, were prone to produce many exceptional progeny.

Bridges conclusion according to these observations were as follows: 1. The exceptional F1 flies were the result of abnormal X chromosome behaviour during meiosis in the females of P generation.

The normal disjoining (separation of the XX chromosomes) did not occur during meiosis. Fertilization of such abnormal eggs would produce zygotes with abnormal number of sex chromosomes.

White-eyed female

Red-eyed male

W+

Normal eggs

Nondisjunctional eggs

nullo-X

W+

W+

W+

W+ XO exceptional Red-eyed male

sperm

XX Red-eyed female

XXX metafemale (usually dies)

XY white-eyed male

XXY exceptional white-eyed female

YO (dies)